CINXE.COM

<!DOCTYPE html><html lang="en-US"><head><title>Just a moment...</title><meta http-equiv="Content-Type" content="text/html; charset=UTF-8"><meta http-equiv="X-UA-Compatible" content="IE=Edge"><meta name="robots" content="noindex,nofollow"><meta name="viewport" content="width=device-width,initial-scale=1"><style>*{box-sizing:border-box;margin:0;padding:0}html{line-height:1.15;-webkit-text-size-adjust:100%;color:#313131;font-family:system-ui,-apple-system,BlinkMacSystemFont,Segoe UI,Roboto,Helvetica Neue,Arial,Noto Sans,sans-serif,Apple Color Emoji,Segoe UI Emoji,Segoe UI Symbol,Noto Color Emoji}body{display:flex;flex-direction:column;height:100vh;min-height:100vh}.main-content{margin:8rem auto;max-width:60rem;padding-left:1.5rem}@media (width <= 720px){.main-content{margin-top:4rem}}.h2{font-size:1.5rem;font-weight:500;line-height:2.25rem}@media (width <= 720px){.h2{font-size:1.25rem;line-height:1.5rem}}#challenge-error-text{background-image:url(data:image/svg+xml;base64,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);background-repeat:no-repeat;background-size:contain;padding-left:34px}@media (prefers-color-scheme:dark){body{background-color:#222;color:#d9d9d9}}</style><meta http-equiv="refresh" content="120"></head><body class="no-js"><div class="main-wrapper" role="main"><div class="main-content"><noscript><div class="h2"><span id="challenge-error-text">Enable JavaScript and cookies to continue</span></div></noscript></div></div><script>(function(){window._cf_chl_opt={cvId: '3',cZone: "www.annualreviews.org",cType: 'non-interactive',cRay: '8e900c37fd1d4030',cH: 'j638YdWvJTO_HjnLCVavdq8ZQ8A7uPLcKwuP97r2JD0-1732688797-1.2.1.1-aDcub87E9XqJhZPHUdRpNpP8Gm53HCsGsIs6AxoZl5JE1QaR1357JHJCvgqXC9FS',cUPMDTk: "\/doi\/10.1146\/annurev-micro-092412-155620?__cf_chl_tk=8T2JbN7vWS7AqxgJvhLEBTQ_EwD7VDbhySzXI7JOQ_g-1732688797-1.0.1.1-B1B3Z3N7CCLWDaXWbL9KQRwwWKUJ3dMoAzHuCg95fZE",cFPWv: 'b',cITimeS: '1732688797',cTTimeMs: '1000',cMTimeMs: '120000',cTplC: 0,cTplV: 5,cTplB: 'cf',cK: "",fa: "\/doi\/10.1146\/annurev-micro-092412-155620?__cf_chl_f_tk=8T2JbN7vWS7AqxgJvhLEBTQ_EwD7VDbhySzXI7JOQ_g-1732688797-1.0.1.1-B1B3Z3N7CCLWDaXWbL9KQRwwWKUJ3dMoAzHuCg95fZE",md: "v.uJZlFgxNQG1G0o3OBi0tmd6fiHf0ScZUJjCcbOq2o-1732688797-1.2.1.1-G8eKqNvFUY1smhSfbKPjqNNMWelCleq4yeWs4UOzMvLfgidWMM1hZWQqyBOs9IYkxxJJfQbrb3SsdWF1k59aLwRjjebMofCGNSfdMEkcO1c71h1.6ahBPGBVHlUWacMDtsbSCzWgOD59Oc3m7VATLu9dFiMY164O8juuS2kY1RxUpLD.gKdXKIN.lHCInkRCCtjRcwL7w1uN2nKle6drwEajcOFZH7T9pmAxHwWiwbPg7RdzIElBj3iL.V_ifveKgc5TzkRcUtZVKnj5Optl9LFmIW8bsLdqrWDlCDs.uCWsjgDXUOjjk180Zo3wFMtnTdcpKqYo9oYBwAZ0YotjjOHmNu.oe35laEhlgOoOr63I1simKek12JM19OHnBJ1kcPxUfmYjZu8mcs5hCMz1x7DbRxb84Hs73pBOSfzukMjFA.k5ATn.4byW5PFXbVPZOkZx8cQX2z1N5Y.3S234f3GV2acFi5X23dYo3.CIkFgm0ntM3RTuFoUhueakLhos4je7kbMIbxtlmsvLZLo2nl_xJc3zkUIn9LQqI2Mp39lAzVBBKvJ7Cmoii1.n4VX5qQheTO5lIxV05I68ztXgsM1IoEHVRpuB3_jskpBhMM6JIuq5CmiWkUyN5tAZn2_KVoFSeCoacGS89It5IfYPT8QaWjATdyC2..hRim5HnhXpnLPtBhWs.pZsoAPAf_r8DYeMU3LkGdhSEPaSsvDxWeNqGkPg69h49VAWrNW.CpHBE_8tIkXG3glvIrL4Q_ZxlJ8lkj23TKzIeRxWkbat3K1IWu2EeRxaorKU9IdmYmJ8zAfpkY366ZnkwjznaVeONB.sdox0M0nb0oMEsxta0FjrjiLeQEttjqbOnMiqpt9sZJZHD9E5Bq9uVhZwPG4xJtwr4wEKIIqDmT227kdWKIjdA3bEbqdxx6enb2wZMxUKn7EOqVTIP74j5B4n4nYtgipTjpaKQq3l9xK6MtZy69wOWLBtiFEhbg_gzK75cPs4XcUY17lZzzO60kFrto1ell7riewX4O0wwIDc9BCLz1cJe53TB38g8COBd6UNDEh.r7OKdVk.zl8tJQD4r_FEXVvtcfPIDI982bzNy5T0R3IDKJosL_wrUdIQtqtpkoXPygWlpSt6fU7U6EMWcJkSNiE5nXS3YDZ_SAxYtxhypLZVFLzt6lSmBCPG8b7W4tDTWVNlRm6FKnVNXAinWladm4JE8ysoBzfZDzSI8xxH4SbYqhktlovEAYbR1.No0.2nyn7t24GQutdepPP0bCA2B2QRxExKtX5UoTv_0u2XtZny.QLxsK6S21ZiBtYpEd3ATjCgrVMYb1OsTQJVCi7W2dz63xUDfh_upecHj3lskWq6y1dghN9aCPBPzTozhybEdHJE67ErJU0fovy4IDiDNZLJ1Q41MhjPw8Ndr4NfrIm2aLC5IBgJsXUYodz3CHw0grHPXZCzF.FBx_kVL2kJr8HPf5kkvz0iJeesay.Eu5.yuJbICnxaX7q7RAWIUpWPpCzc._srgo4TBhbhcZYuDhfax7TsdIMoMypWZt6I2.Ldmp6NmY4L_o9VpDaZdNPj4gJ.PYJxQGqVqTH8kjcGWSaRuRKbfTc8LUBwJHUW4lW3wUibJzzZE7PWkgrOCBcdsNm5Xne0MF62pLG9IvETkmZOWWiAamkFqO2Djf.xZFh.avmDbFQbRs3D0tCbM6hD.mGoEowHdvwSuTjKZtS6QPsKdqWb4g7fJP3QQAbr9LcqOPQPlzDwMPpOO2mTsW6je8scwggouV08X7fqTnLoMSoNoQB9kQ3UKsPgPYfYb4Z6cp8nurN7MUzWOWw8NsjhZbfMk92p02sJ3LehnYKBFXBOdGxlVG_UUT_mnbdFBqPKm6FZawIac.rFBI0C2Gg2tmfevttnKoumcjN22tYMhAqoCXAQ.BtCn3Du4AxDIU3aI1tW5fbgH6yUe76Q.N4SixXSicKXnXW7.BhuqXHsXhsS4s..1Vt4mCAOS6zti5LF.K.y1Wj_QnbGCPfW.tCjm9D8wniZ49rY_fJN.BCa",mdrd: "lvuI8zuyM5FPLsXFP2ADE_5EZDAg.p88LhoxTOkaH2E-1732688797-1.2.1.1-Gmdw1K6RlXLnVZ3NJT8eRxlFCE1PVDvHuzYMnfaMpSSJ.Z.XLzxBQXkMcj90zVEJVbQpNf7wKBM2GEfegekBVCu8YUhgdm3tUfjMxjaRzjBORt5zfG.I16HxDuYcGL7clANzS7_YUs0LrSQhjgFeG9xo3145JIFUS46OH2.sC1nhkubKd4eAI3noQ3E.jPqXdSWe8KAzzBt6l2zL8hKC.U6lP.8PMQNzC7lXzkEyIbJb5UuB_yYYZ5sTXGT28f1nZwEn8w71KXjvxxELcZSKPhy4zPM37QO7qVbJaWDjc.xukE0Cnop0L3zOcSTKBNEpAiEmiIctU.IR.IZfYfspzz_vqc71kGsfXkK0ayCXS56I9gLQPoWVJOJyWkXGKxmdREJ9CY0jCtpwhMp025yFwRaKkLv9hsWFu..7Kwrdft3LvLSA0bPvmvPqqGoAjbBm4lhvzeTaBVh9bPjcJMauRw26.RjKI35Aj_CZ5KjTwEqk5Oq2wpD18skmNexxWHui7HBQJBMtEgdCT_KnINBReGLOUVr3_h4b7V8Z3MvFnSDmjatu2rbIWBXyTOvRIRkDHDas2qoiVll_hl0.ZENJQMDM8hPkDukeZ2vMNbmZntn5OJbEoG_AlqBShDBenoh1bvoocARsLqYqN6tyMDloNNJsFEMPnbtGZxuGiQvPTtGOKUihjHnAL4l1SwU75z13_t.LnbZa7ObI.aNiPJ0YrrRh7W5kJ71nQM7ltl0YItg7MmjxZTfa1NvkOyPy89bse07R8Q0ilsZJX1WsHMfeKgwQ9nU9Z30B6o_QPVD4xVe4TJc44lwwzcCCz2Lfv0IzqvbOSS07VW7j29FEYpjKghDdo5TEqVj3JjCloPwgEfW3vviuMUQyMeqG5.6qUZReICIjh7OQ2DHLrKMPk5BZYFIf4Cg2x4X_1Qw8IpXJlouyX4qwJdIiQfSYwtoCnLbZE6CEe2NKh4yRsqxgEq8buXJyh7FsfTNBGktN5.WLUxqpRBsLkKJEMUdDCDG8Qh27nFPoSh402KqWb4_dRk9Z1w2Lp2O5i8XzKDWMaWkznBpk82a6dWt08xx6GooOl4yQPnntVyo5lrXEjhyhWX1Ftuu5PHOVeaWXSxtGz0AMm4q_Y9JPHTBfYU0upjl8dpwtF_Jm8hXSBY2tsSYlTWG5NjBn4fr2DMTgHoyUvqLka1dzNR.3N9gcSaUScc_rfnls.8MhNr7giaH0zSdrMJFTjPP8zq.azlPOZxBdULTdTmtqB3n7NmXmt9AC797eNKptRGHMUm6q4qvwEbDyO2my7.1RzKGf9GVgtyRuIvxoXF8n1uDodlqrAp_LY.zZQe4ENJft2DggcGl12jdMblRKndlf1YUoXj6lx5x0FX7OIBVZsG4j0A8byWR5CeRWp1SL_s6Tv4MxEy50ijA2Y0Lv4pTZtULbET34PYUMYkBtS28aPkq4w9teUCZJi5vDEKMoKBTACyUsgm5imPF6PgIpIpvSFXw0DrML1589cW941kMAKvo_ec0G5Dgd16Hbmv8uHTijKhklPGlMw._wP71oUyR3PaS3wv8Ba__4B1eCkyHJNt.rSnNDKlIK7kY31pQae.lNUgMENWPji1vpvfhLGrX0Ezkg.oIXMKAT0qkY_ujttDhV.upivqJZpGcxPeWQYywkChq2lw.1R2t_znAMN9zT2lrzg9QNv9QR4XVL5UWfe8giNCC4KNL4cwfsjYWK1QkrsRIw22gdFWgUPgd6UYpdyV8Q8155UX4plI2tD6.WY_Gl6azLylpIdtyaKAEHN.EAEXCdfbO5isCZIlTfJF1A6NzIc7QVKGhvpe_RSCAB9DXpo1Xo6DVzIoO6omDCOv_h_ko.xzG3DvKqTg9Cw84jXALqIoMsGwPPLeIeslCh5fsxvXIaMyTCi3Sfsgg2C8t1JYNOaNGsqbkrjCKYEnrcdbZg1c.S39IuA96guZBFkTd9xgYLNkJhvOGJWBYlJiCyUWP_pV.OqEPNjpeAKQ"};var cpo = document.createElement('script');cpo.src = '/cdn-cgi/challenge-platform/h/b/orchestrate/chl_page/v1?ray=8e900c37fd1d4030';window._cf_chl_opt.cOgUHash = location.hash === '' && location.href.indexOf('#') !== -1 ? '#' : location.hash;window._cf_chl_opt.cOgUQuery = location.search === '' && location.href.slice(0, location.href.length - window._cf_chl_opt.cOgUHash.length).indexOf('?') !== -1 ? '?' : location.search;if (window.history && window.history.replaceState) {var ogU = location.pathname + window._cf_chl_opt.cOgUQuery + window._cf_chl_opt.cOgUHash;history.replaceState(null, null, "\/doi\/10.1146\/annurev-micro-092412-155620?__cf_chl_rt_tk=8T2JbN7vWS7AqxgJvhLEBTQ_EwD7VDbhySzXI7JOQ_g-1732688797-1.0.1.1-B1B3Z3N7CCLWDaXWbL9KQRwwWKUJ3dMoAzHuCg95fZE" + window._cf_chl_opt.cOgUHash);cpo.onload = function() {history.replaceState(null, null, ogU);}}document.getElementsByTagName('head')[0].appendChild(cpo);}());</script></body></html>